Human milk metals and metalloids shape infant microbiota

Background: The profile of metal(loid)s in human milk is essential for infant growth and development, yet its impact on the development of the infant microbiota remains unclear. Elements, such as manganese, zinc, iron or copper, play crucial roles in influencing infant health. Aim: To investigate the metal(loid) content within human milk and its influence on the infant's gut microbiota within the first 2 months after birth. Methods: Human milk samples and infant stool samples from 77 mother-infant dyads in the MAMI cohort were collected at two time points: the early transitional stage and the mature stage. Metallomic profiling of human milk was conducted using inductively coupled plasma-mass spectrometry (ICP-MS). The infant gut microbiota was profiled through 16S rRNA amplicon sequencing and maternal-infant clinical data were available. Spearman's rank correlation coefficientsprovided insights into metal(loid)-microbiota relationships. Results: Independent cross-sectional analyses of mother-infant pairs at two time points, significant variations in metal concentrations and differences in microbial abundances and diversities were observed. Notably, Bifidobacterium genus abundance was higher during the mature lactation stage. During early lactation, we found a significant positive correlation between infant gut Corynebacterium and human milk nickel concentrations, and negative correlations between Veillonella spp. and antimony, and Enterobacter spp. and copper. Additionally, Simpson's diversity was negatively correlated with iron. In the mature lactation stage, we identified eleven significant correlations between metals and microbiota. Notably, Klebsiella genus showed multiple negative correlations with iron, antimony, and vanadium. Conclusion: Our study highlights the significance of metal(loid)-microbiota interactions in early infant development, indicating that infant gut Klebsiella genus may be particularly vulnerable to fluctuations in metal(loid) levels present in human milk, when compared to other genera. Future research should explore these interactions at a strain level and the implications on infant health and development. This trial was registered as NCT03552939.

This research was supported by the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (ERC starting grant no. 639226) and the Spanish Ministry of Science and Innovation (MAMI-Plus ref. PID2022-139475OB-I00); PID2021-123073NB-C21 from the Spanish Ministry of Science and Innovation (MICIN); the Generación del Conocimiento (MCI/AEI/FEDER “Una manera de hacer Europa”), and UHU-1256905 and UHU-202009 from the FEDER Andalusian Operative Program 2014-2020 (Ministry of Economy, Knowledge, Business and Universities, Regional Government of Andalusia, Spain). E.F.V. is grateful for the predoctoral grant awarded by the Spanish Ministry of Science and Innovation and thanks the European Social Fund Plus (ESF+) for the training of doctors within the framework of the State Plan for Scientific, Technical and Innovation Research 2021–2023 (ref. CEX2021-001189-S-20-1). M.B. is grateful for the post-PhD grant “Juan de la Cierva” (ref. JDC2022-050269-I) supported by the Spanish government MCIU/AEI and the European Union “NextGenerationEU”/PRTR. R.C.R. acknowledges the support from the Generalitat-Valenciana for the grant of the Plan GenT project (CDEIGENT 2020). IATA-CSIC authors also acknowledge the Spanish government MCIN/AEI to the Center of Excellence Accreditation Severo Ochoa (CEX2021-001189-S/MCIN/AEI/10.13039/501100011033).

With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2021-001189-S)

Peer reviewed